Infection caused by human herpes simplex virus type 6: causes, symptoms, diagnosis, treatment

Herpesvirus type 6 is considered the most likely etiologic agent of multiple sclerosis, neonatal fever with convulsive syndrome and infectious mononucleosis, Epstein-Barr virus-negative and cytomegalovirus, and HHV-6-associated encephalitis. HHV-6 is a cofactor of AIDS, some forms of carcinoma of the cervix and nasopharyngeal carcinomas.

[1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14]

Epidemiology of infection caused by human herpesvirus type 6

HHV-6, like other herpesviruses, is ubiquitous. Antibodies are detected in the majority (> 90%) of people older than 2 years. At birth, most children are seropositive due to maternal antibodies, whose titre decreases by 5 months. However, by one year the ratio of seropositive children to seronegative is the same as in older children and adults. Maternal antibodies protect against HHV-6 infection in the first months of life, but after a decrease in their titer, the disease may manifest as fulminant exanthema. The virus is in the human body in saliva and nasopharyngeal mucus, in the latent phase it is stored in monocytes / macrophages. In natural conditions, the main way of transmission of the virus is airborne. Sexual transmission of the virus and perinatal infection are also possible. However, in most cases, infection occurs postnatally. It is established that breast milk can not be a transmission factor. Possible infection with blood transfusions, organ transplantation, when using medical instruments contaminated with a virus.

[15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28]

What causes the infection caused by the human herpesvirus type 6?

The human herpesvirus type 6 (HHV-6) is similar to the rest of herpesviruses. But differs from them in biological, immunological properties, the spectrum of sensitive cells, the antigenic structure, the composition of the genome, the number and molecular weight of the structural viral proteins. HHV-6 is assigned to the subfamily Betaherpesvirinae, the genus Roseolovirus.

The diameter of the virion is 160-200 nm, the type of symmetry is ixahedral, the virus contains 162 capsomers, possesses a super-capsid lipid-containing envelope. The genome is represented by double-stranded DNA. Comparison of the primary structure of genomes shows that HHV-6 is more similar to cytomegalovirus than to other herpesviruses.

Studies of HHV-6 isolates from people with various pathologies showed that the viruses belong to variants A or B (HHV-6A and HHV-6B). Infection induced by HHV-6A is less frequent, and the role of this variant of the virus in human pathology is not clear enough, and HHV-6B is considered the main etiopathological factor of the sudden exanthema (Exanthema subitum).

The HHV-6 virus selectively tends towards CD4-T cells, but it is also capable of affecting T cells with CD3, CD5, CD7, CD8 determinants. The virus replicates in many cellular primary and transplant cultures of various origins: T-lymphocytes, monocyte-macrophagal, megakaryocytes, glial cells, thymus cells, in freshly isolated human lymphocytes. The growth cycle of the virus lasts 4-5 days.

Symptoms of an infection caused by the human herpesvirus type 6

The spectrum of diseases associated with HHV-6 is quite wide. HHV-6 is associated with various lymphoproliferative and immunosuppressive diseases, with sudden exanthema of newborns, malignant neoplasms, autoimmune pathology, certain diseases of the central nervous system, etc.

Diseases associated with active HHV-6 infection

Diseases associated with primary acute HHV-6 infection	Diseases associated with persistent HHV-6 infection
Chronic fatigue syndrome (myalgic encephalomyelitis) Sudden exanthema in newborns and children (roseola infantum exanthema subitum) Infectious mononucleosis in adolescents and adults not associated with EBV infection Histiocytic necrotic lymphadenitis (KiKuchis lymphadenitis)	Lymphoproliferative diseases (immunodeficiency, lymphadenopathy, polyclonal lymphoproliferation) Malignant lymphomas (non-Hodgkin's lymphoma, peripheral T-cell leukemia, B-cell lymphoma, dermatopathic lymphadenopathy, lymphogranulomatosis, sinusoidal B-cell lymphoma, pleomorphic T-cell lymphoma)

The etiological role of HHV-6 in the development of sudden exanthema (synonyms: "pink rash of newborns", "exanthema subitum", "roseola infantum", "sixth disease" ICD-10: B08.2), is widely recognized as a widespread disease of children aged 3 months to 3 years. The incubation period lasts 5-15 days. Exanthema subitum is characterized by acute onset, high fever (38.5-40 C) and moderate intoxication. On the 4th day of illness, the temperature decreases, and at the same time or in a few hours a macular rash appears. Usually rashes are localized on the back, abdomen, chest, extensor surfaces of the extremities. On the face, the rash is rare. After 2-3 days the rash disappears without leaving traces. Usually, the disease ends without complications, but clinical cases of a manifest infection that have various symptoms are described: fever above 40 ° C, tympanic inflammation, respiratory and gastrointestinal symptoms, neurologic complications (encephalitis, meningoencephalitis, serous meningitis, convulsions). In rare cases, primary HHV-6 infection occurs with hepatosplenomegaly, fatal fulminant hepatitis, fatal disseminated infection.

Primary infection among adults is rarely detected, it manifests itself in the form of prolonged lymphadenopathy. Mononucleoside-like syndrome, hepatitis, and others.

In the study of peripheral blood, leukopenia, neutropenia, relative lymphocytosis and monocytosis are determined.

The role of HHV-6, as an AIDS cofactor, is provided by its ability to infect, replicate and destroy CD4 cells. The increase of the cytopathic effect in double infection compared with HIV-1 monoinfection is noted, and HHV-6 can both inhibit. And to stimulate the replication of HIV-1.

HHV-6 activates oncoproteins E6 and E7 of human papilloma virus in cervical carcinoma.

HHV-6 DNA was identified in tissues and cells of biopsy specimens of Hodgkin's, mixed B- and T-cell non-Hodgkin's lymphomas. With angioimmunoblastoid lymphadenopathy, African Burkitt's lymphoma, T-cell acute lymphoblastoid leukemia, lymphogranulomatosis, infectious mononucleosis not associated with Epstein on the Barr virus, and a number of other lymphoproliferative diseases.

The role of HHV-6 in the onset of chronic fatigue syndrome is still discussed, and it requires further research.

Diagnosis of infection caused by human herpesvirus type 6

Diagnosis of infection caused by the human herpesvirus type 6 virus is based on the use of immunological methods, electron microscopy and PCR.

[29], [30], [31], [32], [33], [34], [35], [36], [37]

Treatment of infection caused by human herpesvirus type 6

Treatment of infection caused by the human herpes simplex virus type 6 is symptomatic, the efficacy of gancinovir is proven.